Effects of a combination of bedtime intermediate-acting insulin and glibenclamide in type 2 (non-insulin-dependent) diabetic patients with secondary failure to respond to oral hypoglycaemic agents

Abstract

The effect of a subcutaneous injection of an intermediate-acting insulin at bedtime combined with glibenclamide has been evaluated in 16 non-insulin-diabetic patients with secondary failure to respond to oral agents. The patients showed poor metabolic control (HbA1 greater than 11%) after two months on diet and glibenclamide treatment (15 mg.day-1). For 3 months the glibenclamide was continued together with an injection of an intermediate-acting insulin at bedtime in order to maintain fasting blood glucose under 120 mg.dl-1. A significant reduction in fasting blood glucose and HbA1 (15.50 vs 10.35%) and fructosamine (2.03 vs 1.69 mmol.l-1) was observed (230 to 141 mg.dl-1) at a mean insulin dose of 0.28 U.kg-1. The peak blood glucose after a standard test meal was also significantly improved (290 vs 203 mg.dl-1). Two months after the bedtime insulin injection had been withdrawn, only one patient was still being treated with oral agents alone. Except for another patient who dropped out, all the others had to be treated again with insulin because their fasting blood glucose exceeded 180 mg.dl-1. It is concluded that a single subcutaneous injection of an intermediate-acting insulin at bedtime combined with glibenclamide improved fasting and post-meal blood glucose concentrations in non-insulin-dependent patients resistant to diet and oral hypoglycaemic treatment. Almost all of the patients relapsed after insulin was withdrawn.

Overnight GLP-1 normalizes fasting but not daytime plasma glucose levels in NIDDM patients

“…There may be differences between using intermediate-acting insulin (Riddle, 1985;Trischitta et al, 1989;Riddle et al 1989;Yki-Järvinen et al, 1992;Krempf et al, 1992;Shank et al, 1995) and GLP-1 (Rachman et al, 1997;Willms et al, l996a; this study) for the normalization of overnight and morning glycemia. An immediate effect of a standard dose of insulin is difficult to evaluate because of the necessity to approach the clinically effective insulin amount in dose-finding periods.…”

“…One result of these observations is the 'bedtime insulin, daytime oral agent' concept (Riddle et al, 1985;Trischitta et al, 1989;Riddle et al, 1989;Yki-Järvinen et al, 1992;Krempf et al, 1992;Shank et al, 1995). Since, based on previous experience (Nauck et al, 1993c;Weber et al, 1995;Rachman et al, 1996Rachman et al, , 1995Rachman et al, 1997), intravenous GLP-1 infused overnight could be expected to normalize morning (fasting) glycemia, this approach appeared suitable to test whether the reduction in fasting glucose concentrations alone would lead to better glucose profiles over the following 24 h period, after stopping the administration of GLP-1 before breakfast.…”